Abstract

Question

For patients who have had neurosurgery, does enoxaparin (a low-molecular-weight heparin
[LMWH]) used with compression stockings decrease the rate of venous thromboembolism
(VTE) better than compression stockings alone?

Design

Randomized, double-blind, placebo-controlled trial.

Setting

7 Italian neurosurgery centers.

Patients

307 consecutive patients (mean age 56 y, 50% women) who were ≥ 18 years of age with
body weight 40 to 120 kg and who had had elective cranial or spinal surgery. Exclusion
criteria were abnormal operative bleeding, bleeding disorders, need for anticoagulants
or antiplatelet agents, contrast media allergy, renal failure, expected hospital stay
< 7 days, or pregnancy. 84% had venography that was adequate for analysis.

Intervention

All patients wore thigh-length commercial compression stockings from the morning of
surgery until discharge. 153 patients received enoxaparin, 40 mg subcutaneously once
daily starting the day after surgery. 154 patients were allocated to placebo injections.
Prophylaxis duration was 8 days.

Main outcome measures

Main results

Patients who received enoxaparin had lower rates of VTE (all DVT or PE) (P = 0.004), overall DVT (P = 0.004), and proximal DVT (P = 0.04) than did patients who received placebo (Table). The groups did not differ
for 60-day mortality (6 deaths in the placebo group vs 5 in the enoxaparin group, P = 0.8), PE (2 in the placebo group), or for any measure of bleeding (major, minor,
or both, P = 0.2).

Conclusion

Patients who had elective neurosurgery and received compression stockings and enoxaparin
had a lower rate of VTE than patients given stockings alone.

Commentary

This well-done clinical trial complements a similar study by Nurmohamed and colleagues
(1). Both studies show that the combination of LMWH and compression stockings are more
efficacious at reducing venographically documented DVT than stockings alone. These
trials are also important because they have set research standards by including many
patients and by using routine contrast venography rather than the less sensitive,
noninvasive screening tests used in earlier prophylaxis trials in neurosurgery.

A study by Turpie and colleagues (2) showed that sequential compression devices plus stockings provided no more protection
than stockings alone in a broad spectrum of neurosurgery patients. These 3 trials,
therefore, raise concerns about the efficacy of mechanical thromboprophylaxis as the
sole method of prevention in these patients.

The studies by Nurmohamed and Agnelli and their colleagues found trends toward increased
bleeding with administration of LMWH. Before the combination of LMWH and stockings
becomes routine treatment for neurosurgical patients, many more patients must be studied
to provide reassurance that clinically important bleeding is not increased by the
use of LMWH, particularly when it is started within 24 hours of surgery.

The role of the various prophylaxis options in neurosurgery (LMWH, low-dose unfractionated
heparin, compression stockings, pneumatic compression devices, or combinations of
anticoagulant and mechanical prophylaxis) remains unclear. While awaiting further
studies, we will continue to individualize the prophylaxis for these patients based
on the perceived risks for thrombosis and bleeding. For patients at high risk for
bleeding, we use compression stockings and delay the initiation of anti-coagulant
prophylaxis for several days. For patients with increased thromboembolic risk (surgery
for malignancy or motor deficits), we use either low-dose unfractionated heparin or
LMWH.